1. Field of the Invention
Hepatitis B virus (HBV) infection is a world-wide public health problem causing acute and chronic liver diseases including hepatocellular carcinoma. Hepatitis B surface antigen (HBsAg) isolated from the plasma of chronic carries has been extensively studied for immunochemical specificity of the physiologically predominant antigenic determinant a, common to all serotypes of HBsAg, and other subtype specific determinants d/y or w/r, there being a total of ten different serotypes of which four are major. The amino acid sequence of the virally coded HBsAg structural protein of 25,000 daltons has been obtained and the polypeptide sequence associated with the a determinant been defined.
As one outgrowth of this intensive effort is the desire to be able to produce economic, effective, safe vaccines which protect mammalian hosts against the various serotypes of HBV. In developing a vaccine, one wishes to mimic the virulent organism to the greatest degree in the same manner as the virulent organism provokes the natural immunogenic response. At the same time, one wishes to avoid the adverse symptoms resulting from infection. While the determinant site associated with the particular antibodies produced during infection may be only a small portion of a surface protein, the protein may provide the environment and conformation which is specific for the determinant site.
It is, therefore, of great interest to be able to produce relatively small oligopeptides which can serve as haptens to prepare immunogens which provoke a strong immunological response upon injection into a host, so as to act as a vaccine to protect the host from subsequent infection of a microorganism having such a determinant. For hepatitis, it is particularly important to provide for an immunogenic response which produces antibodies specific to the a determinant, so that the host will be immunized against all the serotypes of HBV. It is, therefore, desirable to be able to prepare novel haptenic oligopeptides which can be used for the production of immunogens to be used as vaccines, for the production of antibodies for use in diagnosis or passive immunization or as reagent in diagnostic assays.
2. Description of the Prior Art
Bhatnagar et al., PNAS U.S.A. (1982) 79:4400-4404 describe the HBsAg/adw protein as determined from the gene, various sequences which are shown to be able to compete with the HBsAg for antibodies binding to HBsAg and a list of references providing the historical development of the determination of HBsAg and its determinant sites. See also, Audibert et al., PNAS USA (1982) 79:5042-5046 for a synthetic diphtheria vaccine.